DT-Web

DB00310 - Chlorthalidone


Identification
Name Chlorthalidone
Accession Number DB00310 (APRD00127)
Type small molecule
Description A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 338.766
Groups approved
Monoisotopic Weight 338.012805247
Pharmacology
Indication For management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.
Mechanism of action Chlorthalidone inhibits sodium ion transport across the renal tubular epithelium in the cortical diluting segment of the ascending limb of the loop of Henle. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism.
Absorption Absorbed relatively rapidly after oral administration.
Protein binding High (75% [58% to albumin])
Biotransformation Liver
Route of elimination The major portion of the drug is excreted unchanged by the kidneys.
Toxicity Symptoms of overdose include nausea, weakness, dizziness and disturbances of electrolyte balance.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Deslanoside Possible electrolyte variations and arrhythmias
Diazoxide Significant hyperglycemic effect
Digitoxin Possible electrolyte variations and arrhythmias
Digoxin Possible electrolyte variations and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrythmias
Indacaterol Concomitant therapy may increase the risk of hypokalemia via intracellular shunting. Monitor for adverse effects and especially for cardiovascular effects associated with hypokalemia.
Lithium The thiazide diuretic, chlorthalidone, may increase serum levels of lithium.
Tenoxicam Tenoxicam may antagonize the blood pressure lowering effect of Chlorthalidone. Monitor for changes in the therapeutic effect of Chlorthalidone if Tenoxicam is initiated, discontinued or dose changed.
Trandolapril The thiazide diuretic, Chlorthalidone, may increase the hypotensive effect of Trandolapril. Chlorthalidone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions
  • Take with food (increases availability).

Targets


Solute carrier family 12 member 1
Name Solute carrier family 12 member 1
Gene Name SLC12A1
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.4997

Predictions


Id Partner name Gene Name Score
295 Carbonic anhydrase 1 CA1 0.0632
310 Solute carrier family 12 member 2 SLC12A2 0.0618
357 Carbonic anhydrase 2 CA2 0.0545
170 Succinate semialdehyde dehydrogenase, mitochondrial ALDH5A1 0.0539
592 Carbonic anhydrase 4 CA4 0.0493
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.044
53 Solute carrier family 12 member 5 SLC12A5 0.0343
663 Solute carrier family 12 member 4 SLC12A4 0.0343
304 Solute carrier family 12 member 7 SLC12A7 0.0243
157 Solute carrier family 12 member 6 SLC12A6 0.0242
1729 Solute carrier family 22 member 6 SLC22A6 0.0223
466 Solute carrier family 12 member 3 SLC12A3 0.0222
3932 Glutathione S-transferase A2 GSTA2 0.0201
1405 Thiopurine S-methyltransferase TPMT 0.0178
587 Serum albumin ALB 0.0171
3007 Carbonic anhydrase 12 CA12 0.0147
4205 Carbonic anhydrase 9 CA9 0.0147
1024 Solute carrier family 22 member 11 SLC22A11 0.0133
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0125
20 Prostaglandin G/H synthase 1 PTGS1 0.0122
6142 Solute carrier family 22 member 8 SLC22A8 0.0114
4924 Cytochrome P450 2C8 CYP2C8 0.0106
6016 Cytochrome P450 2C19 CYP2C19 0.0103
4757 Cytochrome P450 2C9 CYP2C9 0.0098
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0095
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0094
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0088
6141 Sodium/bile acid cotransporter SLC10A1 0.0071
118 Organic cation/carnitine transporter 2 SLC22A5 0.0067
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0062
6143 Solute carrier family 22 member 7 SLC22A7 0.0059
290 Prostaglandin G/H synthase 2 PTGS2 0.0055
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0054
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